Project Summary/Abstract Decades of research and clinical observations have established that episodic memory, the ability to remember recently experienced events, depends on the hippocampus and associated structures in the medial temporal lobe (MTL), including entorhinal, perirhinal and parahippocampal cortices [1, 2]. It is thought that the neuronal mechanisms supporting episodic memory for spatial context involves place and grid cells found in the MTL that increase in firing rate when an animal is in a specific location during navigation [3-7]. Furthermore, successful formation and retrieval of spatial memory is thought to be dependent upon the integration of MTL structures through coordinated oscillatory activity related to spike timing dependent plasticity [8-15]. The proposed project will investigate the relationship between spatial navigation, human memory, oscillatory activity, and spatially selective cells using intracranial single-unit and local field potential (LFP) recordings in humans. We will examine patients who are implanted with the Neuropace Responsive Neurostimulator (RNS) or DEPTH electrodes for clinical evaluation and treatment of epilepsy. The RNS device will allow us to stimulate and record LFP activity from the MTL during real world and virtual reality (VR) spatial navigation using simultaneous full body motion capture and immersive VR headset technology. The DEPTH electrodes will allow us to stimulate and record single-unit and LFP activity during immersive VR spatial navigation. Together these studies will have access to over 30 subjects over the project period through an interdepartmental collaboration among clinical and basic science leaders at UCLA. Since our studies address basic questions about the role of oscillations and single neurons in memory, it is anticipated that such basic studies will contribute to bridging of findings between species and laying the scientific foundation for helping future patients with diseases where memory is impaired such as Alzheimer's disease and epilepsy.